Document Detail


Microdialysis monitoring of 3,4-dihydroxyphenylalanine accumulation after decarboxylase inhibition: a means to estimate in vivo changes in tyrosine hydroxylase activity of the rat locus ceruleus.
MedLine Citation:
PMID:  8093483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An on-line microdialysis approach was developed to estimate changes in tyrosine hydroxylase activity in the locus ceruleus noradrenergic neurons of anesthetized rats by measuring the 3,4-dihydroxyphenylalanine (DOPA) accumulation in the extracellular fluid during perfusion of an aromatic amino acid decarboxylase inhibitor through a dialysis probe. The aromatic amino acid decarboxylase inhibitor used was difluoromethyl-DOPA, which was shown to be more stable than NSD 1015 or Ro 4-4602 in the perfusion fluid. A 1-h perfusion of a 10(-4) mol/L of difluoromethyl-DOPA solution induced a linear increase in DOPA concentration in the locus ceruleus dialysates that achieved a steady state within 1 h. The identity of DOPA accumulated in dialysates during aromatic amino acid decarboxylase inhibition was confirmed by the disappearance of the chromatographic peak when DOPA formation was blocked by the administration of alpha-methyl-p-tyrosine. Systemic administration of the alpha 2-antagonist piperoxane before difluoromethyl-DOPA perfusion markedly increased the DOPA concentration during both the accumulation and the steady-state periods, showing that the present technique is a suitable in vivo approach to monitor changes in tyrosine hydroxylase activity occurring in the locus ceruleus neurons.
Authors:
F Robert; L Lambás-Señas; C Ortemann; J F Pujol; B Renaud
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  60     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-02-09     Completed Date:  1993-02-09     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  721-9     Citation Subset:  IM    
Affiliation:
Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, Lyon, France.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Aromatic-L-Amino-Acid Decarboxylases / antagonists & inhibitors*
Benserazide / pharmacology*
Chromatography, High Pressure Liquid
Dialysis / methods
Dihydroxyphenylalanine / analogs & derivatives*,  metabolism*,  pharmacology
Hydrazines / pharmacology*
Kinetics
Locus Coeruleus / enzymology*
Male
Methyltyrosines / pharmacology*
Microchemistry
Rats
Rats, Sprague-Dawley
Time Factors
Tyrosine 3-Monooxygenase / metabolism*
alpha-Methyltyrosine
Chemical
Reg. No./Substance:
0/Hydrazines; 0/Methyltyrosines; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 322-35-0/Benserazide; 63-84-3/Dihydroxyphenylalanine; 637-33-2/3-hydroxybenzylhydrazine; 658-48-0/alpha-Methyltyrosine; 69955-03-9/alpha-difluoromethyl-DOPA; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 4.1.1.28/Aromatic-L-Amino-Acid Decarboxylases

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